Spasticity is characterized by continuous increased muscle tone (resistance), increased spinal reflexes, and involuntary muscle contractions. Spasticity causes muscle tightness, stiff, awkward movements, difficulty while moving, cramping, contractures (tendon shortening), and sometimes painful joints. Spasticity is often accompanied by muscle weakness.
There are a number of known causes of spasticity, tremors, and muscle weakness, including cerebral palsy, traumatic brain and spinal cord injury, stroke, multiple sclerosis, hereditary disorders, metabolic disorders, neurodegenerative diseases, irradiation of the brain and spinal cord, and tumors. Spasticity can also be of idiopathic origin.
Cerebral palsy (CP) is an upper motor neuron (UMN) disorder typically caused by brain injury at or around the time of birth, or in the first year of an infant's life. The most common type of CP is spastic CP, which causes spasticity, mainly of the flexor muscles of the arms and legs. In CP, spasticity is caused by cerebral lesions or UMN lesions in the spinal cord. An undamaged UMN inhibits the motor neurons that innervate skeletal muscles (alpha motor neurons) and the motor neurons that innervate muscle spindles of skeletal muscles (gamma motor neurons). Lesions decrease this inhibitory function of the UMN, resulting in over-activation of the alpha and gamma neurons, particularly in response to reflexes, resulting in spasticity.
FIG. 1 is a schematic illustration of example muscles and nerve fibers involved with spasticity, as is known in the art. FIG. 1 schematically illustrates the following nerve fibers:
(a) an afferent sensory fiber 40, such as a Ia sensory fiber, innervating a muscle spindle 50 of a muscle 14, such as a flexor muscle,
(b) a gamma motor fiber 42 innervating muscle spindle 50,
(c) an alpha motor fiber 44 innervating muscle 14,
(d) a second alpha motor fiber 46 innervating a muscle 15 that is synergistic to muscle 14, and
(e) a third alpha motor fiber 48 innervating a muscle 16, such as an extensor muscle, which is antagonistic to muscles 14 and 15.
All of these nerves terminate in a spinal cord 12 of the subject. Fibers 52 descend from an upper motor neuron (UMN) through spinal cord 12, and have an inhibiting effect on alpha motor fibers 44, 46 and 48, and gamma motor fiber 42.
During a stretch reflex, signals that muscle 14 is stretched are conveyed from muscle spindle 50 over sensory fiber 40 to spinal cord 12. These signals act by means of spinal cord circuitry to stimulate muscles 14 and 15 to contract, and indirectly on alpha motor fiber 48, by means of other spinal cord circuitry, which inhibits signals to antagonistic muscle 16, thereby causing it to relax. These actions combine to produce a coordinated reflex response. In addition, gamma motor fiber 42 “reloads” muscle spindle 50 during active contraction, thereby allowing the spindle to maintain its sensitivity over a wide range of muscle length.
FIG. 2 is a schematic illustration of the example muscles and some of the nerve fibers of FIG. 1, additionally including an example Ib sensory fiber 45, as is known in the art. When muscle 14 is stretched, a Golgi tendon organ 51 stimulates Ib sensory fiber 45. The Ib fiber acts (a) indirectly on alpha motor fibers 44 and 46, by means of spinal cord circuitry, which inhibit the motor neurons of these motor fibers and thereby relax muscles 14 and 15, and (b) indirectly on alpha motor fiber 48, by means of other spinal cord circuitry, which stimulates the motor fiber and thereby stimulates antagonistic muscle 16 to contract.
Current treatments for spasticity and/or CP include physical and occupational therapy, surgery, oral medications, and, more recently, chronic cerebellar stimulation and intrathecal baclofen (ITB) delivered by an implanted pump. Oral medication and physical therapy are generally the first-line treatment for spasticity and/or CP. Controversial treatments include electrical stimulation therapy.
Physical therapy is used to treat spasticity by exercising affected muscles in an attempt to keep joints movable and to preserve the range of motion and flexibility of muscles. Physical therapy for spasticity includes muscle stretching, range of movement exercises, functional retraining, bracing, and splinting. Occupational therapy is used to improve fine motor skills.
In the technique of chronic cerebellar stimulation (CCS), electrodes are implanted on the surface of the cerebellum and are used to stimulate certain cerebellar nerves. Davis R, in “Cerebellar stimulation for cerebral palsy spasticity, function, and seizures,” Archives of Medical Research 31:290-299 (2000), which is incorporated herein by reference, reviews clinical studies of treatment by CCS. He reports that CCS reduced spasticity and athetoid movements in 85% of CP patients treated in eighteen clinics.
Electrical stimulation therapy is a controversial treatment for CP that is generally performed by using very low levels of electrical current to stimulate a desired muscle group to contract. The current is generally applied by electrodes placed on the skin. One type of electrical stimulation therapy, therapeutic electrical stimulation (TES), is administered at night during sleep.
Medications for treating spasticity and/or CP include oral medications such as benzodiazepines (e.g., diazepam and clonazepam), dantrolene, and, more recently, tizanidine (Zanaflex). Additionally, recent studies have shown that injecting Botox (the Botulinum toxin) into spastic muscles can bring relief by causing the muscles to relax.
Lesions decrease the inhibitory function of the UMN by preventing the UMN from sending signals that normally cause the release in the spinal cord of gamma aminobutyric acid (GABA), the most prevalent inhibitory neurotransmitter in the CNS. Baclofen is a medication with a chemical makeup almost identical to GABA. Administered baclofen can partially compensate for the deficiency of natural GABA, thereby treating spasticity. When baclofen is administered orally, a high dosage is necessary in order to achieve an effective concentration in the spinal cord.
PCT Patent Publication WO 01/10432 to Meythaler et al., which is incorporated herein by reference, describes a method for treating spastic disorders, convulsive disorders, pain and epilepsy by administering a therapeutically-effective amount of the compound gamma-aminobutyramide and analogs thereof.
Spasticity has recently been treated with Intrathecal Baclofen (ITB™) therapy, wherein baclofen is introduced directly into the central nervous system (CNS) by an implanted pump. Because baclofen is delivered directly into the spinal fluid, lower dosages are used than those used in oral therapy. Some patients have reported improvements in their conditions as a result of ITB therapy.
Surgery for treating CP includes orthopedic procedures to treat muscle contractures by releasing tendons, and rhizotomy. Rhizotomy is an invasive, irreversible procedure in which a neurosurgeon exposes nerves in the spinal canal that are going to and from muscles in the legs, and cuts about 30 to 50 percent of the dorsal half of each nerve. Spasticity in the legs is often permanently relieved, and, with intensive physical therapy, walking can often be improved. The procedure generally does not treat existing contractures. The procedure is generally considered appropriate only for four-to-seven-year-olds with good leg strength.
U.S. Pat. No. 6,356,784 to Lozano et al., which is incorporated herein by reference, describes techniques for treating movement disorders by stimulating the Pedunculopontine Nucleus (PPN), either electrically and/or by drug infusion. A sensor may be used to detect various symptoms of the movement disorders. A microprocessor algorithm may then analyze the output from the sensor to regulate the stimulation and/or drug therapy delivered to the PPN.
U.S. Pat. Nos. 5,832,932 and 5,711,316 to Elsberry et al., which are incorporated herein by reference, describe an implantable pump and catheter for infusing drugs into the brain to treat movement disorders resulting in abnormal motor behavior. A sensor may be used in combination with the implantable pump and catheter to generate a signal relating to the extent of the abnormal motor behavior. The therapeutic dosage may be regulated in response to the sensor signal so that the dosage is adjusted in response to an increase in the abnormal behavior, so as to decrease the abnormal motor behavior.
U.S. Pat. No. 6,094,598 to Elsberry et al., which is incorporated herein by reference, describes techniques that use one or more drugs and electrical stimulation to treat neural disorders, including movement disorders resulting in abnormal motor response, by means of an implantable signal generator and electrode and an implantable pump and catheter. A sensor is used to detect activity resulting from the neural disorder. A microprocessor algorithm analyzes the output from the sensor in order to regulate the stimulation and drug dosage delivered to the neural tissue.
U.S. Pat. No. 5,833,709 to Rise et al., which is incorporated herein by reference, describes techniques for stimulating the brain to treat movement disorders resulting in abnormal motor behavior by means of an implantable signal generator and electrode. A sensor is used to detect the symptoms resulting from the motion disorder. A microprocessor algorithm analyzes the output from the sensor in order to regulate the stimulation delivered to the brain.
U.S. Pat. No. 4,559,948 to Liss et al., which is incorporated herein by reference, describes cerebral palsy treatment apparatus employing a transcutaneously-applied electric signal to suppress pain and increase motor function. A first positive contact electrode is placed at the frontalis, and a second negative contact electrode is placed at the occiput of the head. Alternatively, the first positive contact electrode is placed at the cervical spinous process and the second negative contact electrode is placed at each affected muscle. An electric signal comprising relatively high frequency pulses with a low frequency amplitude modulation is then applied between the first and second electrodes.
U.S. Pat. No. 5,540,734 to Zabara, which is incorporated herein by reference, describes techniques for treating medical, psychiatric or neurological disorders by applying modulating electric signals to one or both of the trigeminal and glossopharyngeal nerves of a patient. The disorders described as being treatable, controllable or preventable by such nerve stimulation include motor disorders, Parkinson's disease, cerebral palsy, spasticity, chronic nervous illnesses and involuntary movement.
U.S. Pat. Nos. 5,178,161 and 5,314,495 to Kovacs, and U.S. Pat. No. 4,632,116 to Rosen, which are incorporated herein by reference, describe the use of microelectrodes to interface between control electronics and human nerves.
U.S. Pat. No. 4,649,936 to Ungar et al., which is incorporated herein by reference, describes an electrode cuff for placement around a nerve trunk, for generation of unidirectional propagating action potentials.
U.S. Pat. No. 5,199,430 to Fang et al., which is incorporated herein by reference, describes implantable electronic apparatus for assisting the urinary sphincter to relax.
U.S. Pat. No. 4,628,942 to Sweeney et al., which is incorporated herein by reference, describes an asymmetric, shielded, two-electrode cuff for stimulating a nerve.
U.S. Pat. No. 4,019,518 to Maurer et al., which is incorporated herein by reference, describes methods for using an electrical stimulation system to selectively stimulate portions of the body.
Many patents disclose other methods and devices for sensing muscular contractions and for applying muscular stimulation, including: U.S. Pat. No. 6,091,977 to Tarjan et al., U.S. Pat. No. 6,104,960 to Duysens et al., U.S. Pat. No. 6,086,525 to Davey et al., U.S. Pat. No. 4,926,865 to Oman, U.S. Pat. No. 4,392,496 to Stanton, and U.S. Pat. No. 6,146,335 to Gozani, which are incorporated herein by reference.
U.S. Pat. No. 6,119,516 to Hock, which is incorporated herein by reference, describes a biofeedback system, optionally including a piezoelectric element, which measures the motions of joints in the body.
U.S. Pat. No. 5,069,680 to Grandjean, which is incorporated herein by reference, describes the use of a piezoelectric crystal as a muscle activity sensor.
A number of techniques are known for inhibiting or stimulating motor nerves controlling muscular or glandular activities. These include collision blocking, high frequency blocking, and anodal blocking.
In collision blocking, a unidirectional action potential is induced by external electrodes to travel towards the muscle or gland being controlled. These electrode-generated action potentials collide with, and thereby block, the body-generated action potentials.
U.S. Patent Application Publication 2002-0099419 corresponding to U.S. patent application Ser. No. 09/824,682 to Cohen and Ayal, and PCT Patent Publication 02/58782 to Cohen and Ayal, both entitled, “Method and apparatus for selective control of nerve fibers,” and assigned to the assignee of the present patent application and incorporated herein by reference, describe a method particularly useful for pain control. The propagation of body-generated action potentials traveling through a nerve bundle is selectively blocked by using a tripolar electrode device to generate unidirectional action potentials which block, by collision blocking, the body-generated action potentials representing pain sensations in the small-diameter sensory fibers. In the described preferred embodiments, a plurality of electrode devices spaced along the length of the nerve bundle are sequentially actuated with inter-device delays corresponding to the velocity of propagation of the body-generated action potentials through the large-diameter fibers to produce an effect analogous to a wave of green traffic lights, which minimizes undesired anodal blocking of the large-diameter fibers while maximizing the collision blocking of the small-diameter fibers.
In high frequency blocking, high frequency (e.g., 600 Hz) stimulations are used to block the transmission of action potentials through the blocked nerve fibers.
In anodal blocking, nerve fibers are locally hyperpolarized by anodal current. If sufficiently hyperpolarized, action potentials are not able to propagate through the hyperpolarized zone and are blocked.
The anodal block has been investigated for producing selective blocking of the action potentials through selected motor nerve fibers, particularly the larger-diameter nerve fibers which are more sensitive to the hyperpolarization. Unblocked electrode-generated action potentials (or those blocked to a lesser degree) passing through the anodal block generate collision blocks. These collision blocks enable the selective control of motor nerve fibers in order to stimulate or suppress, as the case may be, selected muscular or glandular activities. See, for example, van den Honert C et al., “A technique for collision blocks of peripheral nerve: single stimulus analysis,” IEEE Transactions on Biomedical Engineering, 28(5), 373-378 (1981), which is incorporated herein by reference.
A number of patents and articles describe methods and devices for stimulating nerves to achieve a desired effect. Often these techniques include a design for an electrode or electrode cuff.
U.S. Pat. No. 4,608,985 to Crish et al., which is incorporated herein by reference, describes electrode cuffs for selectively blocking orthodromic action potentials passing along a nerve trunk, in a manner intended to avoid causing nerve damage.
PCT Patent Publication WO 01/10375 to Felsen et al., which is incorporated herein by reference, describes apparatus for modifying the electrical behavior of nervous tissue. Electrical energy is applied with an electrode to a nerve in order to selectively inhibit propagation of an action potential.
U.S. Pat. No. 5,755,750 to Petruska et al., which is incorporated herein by reference, describes techniques for selectively blocking different size fibers of a nerve by applying direct electric current between an anode and a cathode that is larger than the anode. The current applied to the electrodes blocks nerve transmission, but, as described, does not activate the nerve fibers in either direction.
The following articles, which are incorporated herein by reference, may be of interest:
Ungar I J et al., “Generation of unidirectionally propagating action potentials using a monopolar electrode cuff,” Annals of Biomedical Engineering, 14:437-450 (1986)
Sweeney J D et al., “An asymmetric two electrode cuff for generation of unidirectionally propagated action potentials,” IEEE Transactions on Biomedical Engineering, vol. BME-33(6) (1986)
Sweeney J D et al., “A nerve cuff technique for selective excitation of peripheral nerve trunk regions,” IEEE Transactions on Biomedical Engineering, 37(7) (1990)
Naples G G et al., “A spiral nerve cuff electrode for peripheral nerve stimulation,” by IEEE Transactions on Biomedical Engineering, 35(11) (1988)
van den Honert C et al., “Generation of unidirectionally propagated action potentials in a peripheral nerve by brief stimuli,” Science, 206:1311-1312 (1979)
van den Honert C et al., “A technique for collision block of peripheral nerve: Frequency dependence,” MP-12, IEEE Trans. Biomed. Eng. 28:379-382 (1981)
Rijkhoff N J et al., “Acute animal studies on the use of anodal block to reduce urethral resistance in sacral root stimulation,” IEEE Transactions on Rehabilitation Engineering, 2(2):92 (1994)
Mushahwar V K et al., “Muscle recruitment through electrical stimulation of the lumbo-sacral spinal cord,” IEEE Trans Rehabil Eng, 8(1):22-9 (2000)
Deurloo K E et al., “Transverse tripolar stimulation of peripheral nerve: a modelling study of spatial selectivity,” Med Biol Eng Comput, 36(1):66-74 (1998)
Tarver W B et al., “Clinical experience with a helical bipolar stimulating lead,” Pace, Vol. 15, October, Part II (1992)
Agnew W F et al., “Microstimulation of the lumbosacral spinal cord,” Huntington Medical Research Institutes Neurological Research Laboratory, Sep. 30, 1995-Sep. 29, 1998.
In physiological muscle contraction, nerve fibers are recruited in the order of increasing size, from smaller-diameter fibers to progressively larger-diameter fibers. In contrast, artificial electrical stimulation of nerves using standard techniques recruits fibers in a larger- to smaller-diameter order, because larger-diameter fibers have a lower excitation threshold. This unnatural recruitment order causes muscle fatigue and poor force gradation. Techniques have been explored to mimic the natural order of recruitment when performing artificial stimulation of nerves to stimulate muscles.
Fitzpatrick et al., in “A nerve cuff design for the selective activation and blocking of myelinated nerve fibers,” Ann. Conf. of the IEEE Eng. in Medicine and Biology Soc, 13(2), 906 (1991), which is incorporated herein by reference, describe a tripolar electrode used for muscle control. The electrode includes a central cathode flanked on its opposite sides by two anodes. The central cathode generates action potentials in the motor nerve fiber by cathodic stimulation. One of the anodes produces a complete anodal block in one direction so that the action potential produced by the cathode is unidirectional. The other anode produces a selective anodal block to permit passage of the action potential in the opposite direction through selected motor nerve fibers to produce the desired muscle stimulation or suppression.
The following articles, which are incorporated herein by reference, may be of interest:
Rijkhoff N J et al., “Orderly recruitment of motoneurons in an acute rabbit model,” Ann. Conf. of the IEEE Eng., Medicine and Biology Soc., 20 (5):2564 (1998)
Rijkhoff N J et al., “Selective stimulation of small diameter nerve fibers in a mixed bundle,” Proceedings of the Annual Project Meeting Sensations/Neuros and Mid-Term Review Meeting on the TMR-Network Neuros, Apr. 21-23, 1999, pp. 20-21 (1999)
Baratta R et al., “Orderly stimulation of skeletal muscle motor units with tripolar nerve cuff electrode,” IEEE Transactions on Biomedical Engineering, 36(8):836-43 (1989).
The following articles, which are incorporated herein by reference, describe techniques using point electrodes to selectively excite peripheral nerve fibers:
Grill W M et al., “Inversion of the current-distance relationship by transient depolarization,” IEEE Trans Biomed Eng, 44(1):1-9 (1997)
Goodall E V et al., “Position-selective activation of peripheral nerve fibers with a cuff electrode,” IEEE Trans Biomed Eng, 43(8):851-6 (1996)
Veraart C et al., “Selective control of muscle activation with a multipolar nerve cuff electrode,” IEEE Trans Biomed Eng, 40(7):640-53 (1993)